| First Author | Vanickova K | Year | 2023 |
| Journal | EMBO J | Volume | 42 |
| Issue | 23 | Pages | e113527 |
| PubMed ID | 37846891 | Mgi Jnum | J:343307 |
| Mgi Id | MGI:7563790 | Doi | 10.15252/embj.2023113527 |
| Citation | Vanickova K, et al. (2023) Hematopoietic stem cells undergo a lymphoid to myeloid switch in early stages of emergency granulopoiesis. EMBO J 42(23):e113527 |
| abstractText | Emergency granulopoiesis is the enhanced and accelerated production of granulocytes that occurs during acute infection. The contribution of hematopoietic stem cells (HSCs) to this process was reported; however, how HSCs participate in emergency granulopoiesis remains elusive. Here, using a mouse model of emergency granulopoiesis we observe transcriptional changes in HSCs as early as 4 h after lipopolysaccharide (LPS) administration. We observe that the HSC identity is changed towards a myeloid-biased HSC and show that CD201 is enriched in lymphoid-biased HSCs. While CD201 expression under steady-state conditions reveals a lymphoid bias, under emergency granulopoiesis loss of CD201 marks the lymphoid-to-myeloid transcriptional switch. Mechanistically, we determine that lymphoid-biased CD201(+) HSCs act as a first response during emergency granulopoiesis due to direct sensing of LPS by TLR4 and downstream activation of NF-kappaBeta signaling. The myeloid-biased CD201(-) HSC population responds indirectly during an acute infection by sensing G-CSF, increasing STAT3 phosphorylation, and upregulating LAP/LAP* C/EBPbeta isoforms. In conclusion, HSC subpopulations support early phases of emergency granulopoiesis due to their transcriptional rewiring from a lymphoid-biased to myeloid-biased population and thus establishing alternative paths to supply elevated numbers of granulocytes. |
